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NMDA receptor antagonists


Ricardo
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     Forgive me if some of this is repetitive, much of this has been posted on our Ketamine thread, but I felt like it deserved a thread of it's own. 

Ever since I ended up in the ER with a cluster and they gave me I.V. magnesium I have been interested in glutamate toxicity in the brain.  I couldn't believe it actually worked.  The doc told me it would help by relaxing the muscles in my head, After some research I think it may have actually helped by blocking glutmate toxicity in the brain, in other words by it's NMDA receptor antagonist properties.   I highly encourage people to try out intravenous magnesium instead of triptans or opiates if you end up at the ER, I'm inclined to think (assuming it works for you) that it would be less likely than other options to give you a rebound.  Then again, trying to go into the ER and telling them what to give you is not always be easy :)

So I'll start with a good article on glutamate that I came across from the Dana institute.  It is mostly about head trauma and strokes, but it has a lot of good info on glutamate toxicity and some ideas on how to treat it.

http://www.dana.org/news/cerebrum/detail.aspx?id=7376

  High levels of glutamate in peoples cerebral spinal fluid (CSF) have been found in chronic migraine and fibromyalgia, Chronic Daily Headache, and glutamate toxicity has been implicated in MS.  As of yet I have not been able to find any info on glutamate CSF levels in cluster sufferers.

http://www.ncbi.nlm.nih.gov/pubmed/15315529

http://www.ncbi.nlm.nih.gov/pubmed/12662182

    Ketamine is one well known NMDA receptor antagonist, and in a study that the great Dr. Andrew Sewell posted on our Ketamine page just last week it shows that it has promise for migraines, paroxysmal hemicrania, Chronic Daily Headache, and clusters...Here's some of the study he cited...(check out the Ketamine thread for his full post)

"IV ketamine resulted in substantial benefits in all patient groups. Among the refractory migraine group, 93% had greater than 50% reduction in pain intensity. All cluster headache patients had complete resolution of their ongoing cluster episodes (average of 6.4 days). Four of 4 paroxysmal hemicrania patients had complete resolution of headaches (average of 7 days). Sixty-eight percent of chronic daily headache patients and 80% of patients with headache and facial pain were reported to have more than 50% improvement in their pain patterns (exact definition of improvement not provided). Side effects of ketamine infusion included a transient sense of calmness and lightheadedness, experienced by 41% of patients. No patients fell asleep, became dysphoric, or experienced hallucinations. Investigators concluded that IV ketamine is safe and effective for the outpatient treatment of several refractory headache disorders."

  Interesting enough, here's a link showing that "Glutamate may be implicated in triptan response mechanisms, triptans may work in part by reducing extracellular glutamate levels in the brain."

http://www.ncbi.nlm.nih.gov/pubmed/17578532

And....a whole bunch more sometime when I don't have to work...

Anybody else out there have any ideas or thoughts on this?  Anybody tried I.V. magnesium for their clusters?

-Ricardo

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Anybody tried I.V. magnesium for their clusters?

I talked a doctor into giving me a magnesium sulfate I.V. once with great expectations.

I had to pull over on the way home from the I.V. and whip out an injector. The I.V. did nuthin' whatsoever for me.  :-?

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I really worked for getting intravenous magnesium here where i live. Impossible. When i ask why i get the answer it`s so risky. But a cocktail (the word they actually use for it) containing Pred and this and that of variuous things with bad sideeffects, that`s not risky? Then i got the aswer "it`s just the way it is in Norway". Irrititating, i want to try.

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  • 5 weeks later...

Here's a wikipedia article on NMDA receptor antagonist with a list of some of the known drugs in the class. 

http://en.wikipedia.org/wiki/NMDA_receptor_antagonist

Obviously, not all of them are going to help, One of the drugs listed is alcohol!  Some of them are already used for clusters like Tramadol and Mementine, but I haven't heard really great results from people that have tried them...maybe I just haven't talked to the right people.  The ones that seem to me like they might have promise are Orphenadrine, Ketamine, Nitrous Oxide, Dextromethorphan  (actually found a doc on line recommending mixing up the trex with some Dextromethorphan) and I.V. magnesium.

According to the article I posted by the Dana institute, your brain's ability to remove excess glutamate is largely dependant on the amount of glutamate in your blood.  If the levels are too high in your blood your brain is not able to rid itself of excess glutamate.  With this in mind, I think a couple things to get your blood glutamate levels lower could include lots and lots and lots of water (Many people including myself find this to be helpful with some clusters) and eating less high glutamate foods.  A while back I had a list of high and low glutamate foods, I'll try and find it.

In that same Dana Institute link they talk of a novel way of reducing the glutamate in both the brain and the blood by an I.V. solution of a natural compound called oxaloacetate.  Supposedly it transforms the glutamate into another substance, lowering the blood glutamate levels first, then the brain.  Right now I'm looking into Pyruvate supplements...Pyruvate carboxylase catalyzes to form oxaloacetate and although I have not been able to find Pyruvate carboxylase supplements, I have seen calcium pyruvate.  The little research I've done leads me to think it will do the same thing, but as of right now I'm not sure. I'll keep looking and keep ya'll posted.

-Ricardo

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  • 1 month later...

Hi all thanks for the support you gave me! Ricardo said something about alcohol as NMDA receptor antagonist.

My CH started 2yrs ago cronic since then was only diagnosed in June was put on prednisone and verapamil it didnt help. Dr said then I am "snookered" nothing will help! Got myself some O2 and drank coffee. Tried D3etc didnt help.Tried licorice, it did change everything night attacks stopped and shifted to daytime but what a nice good mood! It still has an effect on me for bad or worse I am so darn honest now and I can scream of it!

Last teusday my husband mentioned my CH to a GP and he said it was something I stopped or started doing. 2yrs ago I stopped drinking beer. Teusday evening I drank beer again and since then no night HA again still get shadows during the day but nothing like the past.

Read it has to do with delirium tremens that causes an "adrenergic storm" and the treatment is diazepam. Today I went to that GP but he wants to treat me with amitriptyline that is a serotinin-norepinephrine reuptake inhibitor. What do you clever guys think?

Was on the point to order mushrooms but got Rynauds disease was scared and dont have green fingers!

Painfree days to you all!!

heilette

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So.....Let's see if we can tease this apart.   Alcohol IS an NMDA receptor antagonist, but it has many other actions, most of them very bad for headache.  These "bad" actions that have to do with headache greatly outnumber the "good" of NMDA antagonist.  Alcohol is almost always bad for a headache, I'm guessing it COULD be helpful with tension headaches, but I wouldn't bet on it.  Beer is a completely different thing, mostly from the Hops.  If you really think the beer is helping, you could try hops on it's own.  It does have some pain killing properties, sedative properties (is it helping you sleep better, which gives you less headaches?),  and probably some anti-inflamatory action...But then again if beer works, beer works, right?  :)

Unless you get to the "Delerium Tremens" thing.  That's when you become delirious from your body going through withdrawal after becoming addicted to alcohol and you stop drinking.  I'm guessing you don't have that, but hey, no judgement here :)  And if you DID have delerium tremens, another beer might not be what you want ;)

Last note... As far as I know, Amitriptyline has been shown to be successful with migraines but I've never heard of it working for clusters.

-Ricardo

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if i can say so, heilette, this sure seems like a lot of questionable medical advice. i'm not a doctor or even one of the clever guys, but . . . try two things and you're "snookered"?  nah.  and i'd say that it's quite unlikely that something you started or stopped doing two years ago caused your attacks.  possible, i suppose, but unlikely.  (of course, as ricardo says, if beer works, then beer works, and it's good you've found it.)

no imitrex?  the oxygen is helping, or no?  (if no, then maybe, given all your other information, you don't have CH and you need a better diagnosis.)

do you have access to "energy drinks" such as RedBull or Monster brands -- it's generally believed that the taurine in those drinks (which also contain a lot of caffeine, as with your coffee) helps with CH.  some people take taurine capsules.

have you tried melatonin?

hard to guess why the licorice root would cause that shift.  maybe you could send a private message (a PM) to les genser (who developed the licorice root regimen) and ask him about it -- though he hasn't been here much lately.  you can pm him from here: http://www.clusterheadaches.com/cb/cgi-bin/yabb2/YaBB.pl?action=viewprofile;username=41485E724A48435E485F2D0

be careful with the licorice root (maybe especially in light of your raynaud's).  les cautioned that it shouldn't be taken in high doses for extended periods of time.  here's some information about all that: http://www.clusterheadaches.com/cb/cgi-bin/yabb2/YaBB.pl?num=1298659068

it's not clear, from the very small amount that i know about raynaud's, how the raynaud's would interact with psychedelics, and the reasons for your concern.  can you say a little more about that?  if certain kinds of seeds (rivea corymbosa or hawaiian baby woodrose, particularly) can be purchased there, then your lack of growing skill might not be an obstacle to busting.

and, broken record that i am on this topic, i'd just like you to be sure that you were doing correct dosages of the vitamin D3, and that you gave it enough time.  dosages are listed here: http://www.clusterheadaches.com/cb/cgi-bin/yabb2/YaBB.pl?num=1314134804

hopefully, the truly clever folks will be here with more, and better.

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i was on cymbalta (another snri) before i started busting

and found that it was helping in dealing with

the pain.

if you are not planning on using psychedelics for busting

i would give the new med a go. esp if you end up with a diagnosis of

hemecrania continum (spelling?). as the snri's show good promose in

helping with that type of head pain.

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Thanks Ricardo I never got the delirium tremens thing. Perhaps I must first try the Hops on its own.

Thanks CHfather I think the diagnose is correct. The HA woke me up at night 1 1/2 hours after going to bed, eyelid dropping and red, nose blocked on right side pain behind eye and marching the kitchenfloor for 30min then the pain was gone. Later 3 attacks per night. After the verapamil everything was worse my whole head had this "cold sensation/shadow" all the time. O2 only worked for the first 2attacks not the rest but then it was morning again and the coffee helped. The imitrex nasal is still in its packet havent tried it after the side-effects of the verapamil. Was on the verapamil when first tried the D3. Have tried the RedBul but my tummy doesnt "like" it I rather stay with the coffee.

I followed les doses it didnt have an effect on my raynauds. read about raynauds in the warning for busting, never knew why my fingers go white but making it warm in hot water makes it go away.

Now I am so PF I dont know what to do my whole idea was to stop drinking 2yrs ago!!

Thanks

heilette

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I think it is smart of you to go slowly with the psychedelics seeing as you have been diagnosed with Raynaud's....Raynaud's syndrome is essentially a problem with blood flow to your extremities...Vasodilators will help, vasoconstricters will make it worse.  Most Tryptamine psychedelics (mushrooms and LSA containing seeds like the RC seeds) are vasoconstricters, meaning they could make the situation worse.  Although I don't have any real info in front of me, for some reason I think the seeds may actually have MORE vasoconstriction than the shrooms, but I'm not 100%.  I would try a small bit...like a REAL small bit first and see if it starts making your symptoms worse.  I would also go heavy duty on ginger, it's a pretty potent vasodilator AND it'll help with nausea, could even help to abort a cluster.

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Yesterday I went to the dentist to have 2 cavities filled and a small mouth guard made that might help with clenching in my sleep (Surprised to find that it is FDA approved for migraines....)  I almost canceled, my head was not feeling so great.  Admittedly, it was not what I would consider a typical cluster, and more and more I'm starting to think I may have migraines or HC along with my clusters, but this was an interesting experience nonetheless. 

The interesting part came when they put the nitrous oxide mask on me.  Within minutes (maybe less) my headache was gone.  100%.  They kept the mask on me for about 2 hours, the whole time I was pain free, and the relief lasted for the rest of the night.  A brief shadow emerged at one point, but very brief and very light.

Gives a little more credence to this account:

http://www.erowid.org/experiences/exp.php?ID=23397

Side note-Batch has pointed out that the mixture with Nitrous Oxide is actually half oxygen.  Although this would seem like a no-brainer that the O2 was what as actually aborting the pain, I have tried O2 at 65 LPM with a non-rebreather mask for 20 min with no relief.  Also, I have not heard of many people that can abort with O2 in somewhere around  30 seconds.

Here's another link--http://www.nature.com/nm/journal/v4/n4/abs/nm0498-460.html

Best part--my dentist told me to call up when I'm getting hit and I can try out the Nitrous without any dental work   :)

-Ricardo

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After thinking about how much it's going to suck to have a raging headache, hope it's during my dentist working hours, drive down there and suck down some of their Nitrous, I figured I would go a different route.  Seeing as how the Ketamine has gotten me off the zomig and I'm not paying $60 a month in copays for it, I figured this might be worth it.  Worse case scenario I'll end up getting high off Nitrous for a while and even get to see if I can make some coconut milk whipped cream.    Just ordered, I'll keep ya'll updated!

http://www.webstaurantstore.com/1-2-liter-whip-cream-dispenser-white/407WHC16%20%20%20%20WHT.html?

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Hi Ricardo,

My best friend since childhood is a dentist and has offered to hook Michael up with the nitrous to see if it works for him. We haven't taken him up on the offer yet but after your experience I think maybe we'll go in tomorrow. Michael hasn't had any PF time for a couple of months - maybe more - so we're anxious to find if it'll work. If it does, I'm going to find a way to keep some on hand.

Ron

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I'm still kinda amazed how well the Nitrous at the Dentist worked for me.  That day my beast was rearing it's head in that way that tells me I'm usually screwed for the day.  The nitrous from the whipped cream maker, however, was not too effective.  Actually it was REALLY effective, but only lasted less than a minute, then it all came back.  Oh well...I'm betting the real effectiveness that I got from the dentist was from the 2 hour long nitrous mask and my brain being bathed in NMDA receptor antagonist goodness...

Unfortunately, it has had one sinister side effect.  An addiction that Ricardo thought was long gone has resurfaced with the use of the "Hippy Crack".  I thought I was fine.  It's been years and years.  I gave up many many things at one point in my life, around the time I found out I had to give up gluten and dairy.  Yup.  You guessed it---the coconut milk whipped cream is friggin awesome and I can't stop myself.  It brings me back to my debauchery days of 8 years old, repeatedly spraying the frothy sweet cream over donuts, sandwiches, cookies, you name it.  My only hope now is to up the amount of mushrooms and pray for salvation.  Until then, I am drinking 6 times as much coffee because it's just so damn good with whipped cream.

-Ricardo

PS--after that post, I think I will change my mood to "Strange" forever :)

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  • 2 months later...

Finally! Got Mike to my dentist friend's office today and gave nitrous a whirl. Sadly, it didn't appear to have any effect save getting him high as a kite - which he thoroughly enjoyed. We kept cranking up the nitrous on the oxygen/nitrous mixture over the course of 20-30 minutes. He got higher and higher but it never had any effect on his HA. Too bad. So sad. Mike's dad.

Ron

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  • 7 months later...

Another interesting experience with the dentist.  This time I was going for 2 cavities filled.  I had just busted with high dose mushrooms about 6 days before and was finally feeling like my clusters that always come out hard at this time of year had faded.  When I went into the dentist, no cluster at all.  She got me all set up and injected the novicaine/ephedrine (how many people are aware that pretty much ALL novicaine they inject you with also has ephedrine?  I didn't until recently...)  The shot hurt like hell at first (like usual) then everything went crazy.  She obviously hit a nerve with either the needle or just the novicaine mixture, because I had white hot fire trace the entire nerve from the point of injection, up through my face and into my eye.  Immediate kip 9 in my right eye.  I sat bolt right up and started hyperventilating--the look on the dentists face was absolute horror, she had no idea what was going on.  In between breaths I explained that a heavy duty cluster was in full swing and she went to get me ice.  Strangest of all, was that my eye went completely numb--yet I still had a kip 9 in that eye.  How does that make any sense at all?  Reminds me of the story about the guy that had his trigeminal nerve severed and STILL got clusters...The dentist gets back with ice and put it to my head.  Unfortunately, it did absolutely nothing, because my eye was completely numb and not feeling the cold.  I think I started getting kinda crazy, the whole situation was so surreal--ridiculous pain and completely numb at the same time in the same place, I started to laugh thinking "WTF is going on?!?  Is this a dream?  If it is, it's a pretty shitty dream..."  while rocking back and forth in miserable pain.  Now I can't see straight because my numb eye can't focus, and I'm trying to (unsuccesfully) wrestle my Imitrex injector out of my murse.  Luckily by now the dentist had the nitrous tank set up and put the mask on.  Within less then a minute the pain faded, within 5 it was gone for most of the day.  Thank god for Nitrous. 

It unfortunately did not have the same long term effect that I got the last time I received heavy duty nitrous, and I found myself in a heavy duty cluster cycle within a day or 2.  One of the days I found myself getting hit hard at work, by the time I got home and made some mushroom tea I was a wreck, could hardly stand and was so ready to puke it wasn't funny.  Worst part about getting all pukey is that I KNOW I'm not going to be able to keep the shroom tea down long enough for it to work it's magic and abort my cluster, so I got out my whipped cream charger and inhaled 3 cartridges worth of nitrous.  Instant, complete relief that only lasted a few minutes, but when it wore off my cluster was at a kip 4-5 instead of 8-9, and no more nausea.  I drank my tea, busted my cluster and have been much better since then. 

A long week indeed.  At least now I know no dentist ever touches my teeth again without hooking me up to a nitrous tank first.

-Ricardo

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Carlos,

I think you are talking about epinepherine (EPI), instead of ephedrine.  EPI can and usually will trigger a cluster.  I know, I found out the hard way.  Luckily, my dentist had an oxygen tank with a high flow regulator. 

There are other options to local anesthetics used by dentist that don't contain EPI.  I believe one of them is called Prilocaine.  I highly recommend anyone with clusters letting their dentist know and requesting them not to use EPI!

I found the following article by Dr. Ron Briglia:

[highlight]"The ingredient that causes the most reactions in patients is the epinepherine that is part of some local anesthetics.

In order to keep teeth numb for long dental procedures or to stop bleeding around the gum of a tooth that is going to be restored, the epinepherine in the local anesthetic constricts blood vessels in the area where it is injected.

The reason is two fold: First, the epinepherine constricts blood vessels which stops any bleeding in the area. Second, it prevents the blood stream from diluting and transporting the anesthetic away from the area thus keeping the tooth numb for long appointments.

The body is a wonderous thing because it detects that somewhere in the body that some blood vessels are getting constricted. The brain senses this and sends out signals to the heart to start pumping faster and harder to "open" these constricted blood vessels.

This is the reaction that most dental patients think is an allergic or bad reaction to the anesthetic.

At this point a patient may feel like their heart rate has increased or that they feel a little lightheaded. After about 30-60 seconds your body adjusts to the epinepherine effects of the local anesthetic and the heart rate returns to normal.

For patients who are overly sensitive to the effects of epinepherine, there are many local dental anesthetics without this ingredient added."[/highlight]

http://www.dental--health.com/novacaine4.html

I hope this helps you and others.  As you now know, it's no fun getting hit in the dentist chair. :'(

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